Search Results (32)

The assessment of the ovarian reserve is important in patients with fertility intent. The anti-Müllerian hormone (AMH) serum level is a useful ovarian reserve marker. Endometriosis is a benign disease with three phenotypes: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep endometriosis (DE). Endometriosis is linked with infertility; however, the exact impact of endometriosis and endometriosis surgery on AMH levels is less clear. This narrative review examines how different endometriosis phenotypes and related surgeries affect AMH levels as well as explores whether pre- and post-surgical AMH can predict the reproductive outcomes in women seeking pregnancy. The evidence suggests that OMA is linked to reduced AMH values and a higher AMH decline rate over time. OMA cystectomy causes further a reduction in AMH, which, however, tends to recover postoperatively. Non-excisional surgery for OMA spares the ovarian parenchyma; however, an at least temporary decline in AMH is observed. The effect is likely smaller than that of cystectomy. Non-thermal methods of hemostasis following cystectomy are likely superior in terms of AMH. The AMH levels before OMA cystectomy appear to be positively correlated with the postoperative probability of pregnancy, particularly spontaneous conception, but not livebirth rates. Preoperative AMH levels are also predictive of the risk of diminished ovarian reserve (DOR). Similarly, postoperative AMH levels and the rate of AMH decline at 1 year after OMA cystectomy appear to be predictive of fertility outcomes. SUP likely has little (if any) impact on AMH levels. DE reduces AMH levels, and a further reduction following surgery is anticipated. However, a reduction in AMH values should not be interpreted as a decline in the patient’s reproductive potential. Further research should focus on the extra-ovarian locations of endometriosis and their impact on AMH values. Full article

Exposure to bisphenol A (BPA), one of the most widely produced plasticisers, can have a major effect on the growing embryo and the mother during pregnancy; as this is the most vulnerable period, the cutoff established in the legislation does not take this factor into account. Thus, this narrative review aims to highlight the consequences for the foetus and the pregnant woman of maternal and foetal exposure to BPA by analysing epidemiological and experimental studies on humans. Extensive research has examined the effects of BPA on several systems outcomes. Specifically, BPA exposure affects the immune system of the offspring and promotes the development of respiratory diseases, including asthma and wheezing. Moreover, BPA has been negatively associated with children’s neurodevelopment, leading to behavioural changes; autism; and reproductive changes, mainly deviations in anogenital distance, sexual hormone levels and sexual maturation, which can result in infertility. Furthermore, in mothers, BPA exposure may be linked to pre-eclampsia and gestational diabetes mellitus and affects birth parameters, leading to a higher risk of preterm delivery, shorter birth lengths and lower birth weights, although the results were not always consistent. These results demonstrate the urgent need for stricter legislation banning the use of BPA during pregnancy to reduce the hazards to the health and development of the foetus and the unborn child. Full article

Hyperandrogenism is a determining diagnostic factor for PCOS. If pregnancy is conceived, it is considered high-risk due to several potential complications, but the correlation between pre-pregnancy androgen levels and obstetric outcomes is poorly characterized. Objective: To determine if pre-pregnancy serum androgen concentrations and androgen indexes differed when certain obstetric and neonatal outcomes appeared in PCOS. Methods: A single-center, retrospective study was carried out. All patients were treated between 2012 and 2019. A total of 73 patients had all the endocrine and obstetric data available. Pre-pregnancy hormone levels (total testosterone-T, androstenedione-AD, DHEAS (dehydroepiandrosterone sulfate), SHBG (sex-hormone-binding globulin), and TSH (thyroid-stimulating hormone) were collected, and T/SHBG, AD/SHBG, DHEAS/SHBG, T/AD indexes were calculated and compared. Results: When miscarriage was present in the history, significantly elevated pre-pregnancy AD levels were observed. Higher pre-pregnancy AD level was noted in PCOS patients delivering female newborns as compared to males. Additionally, a higher T/AD ratio was associated with subsequent preterm delivery, but significance was lost after age adjustment. Maternal age at delivery had a significant negative correlation with pre-pregnancy DHEAS levels and DHEAS/SHBG ratio. Pre-pregnancy SHBG displayed a significant negative correlation, while pre-pregnancy androgen/SHBG ratios exhibited positive correlations with both birth weight and birth weight percentile. Conclusions: Based on our data, AD and the T/AD ratio emerge as distinctive factors in certain outcomes, implying a potential specific role of altered 17-β-HSD (17β-hydroxysteroid dehydrogenase) enzyme activity, possibly influencing offspring outcomes. The pre-pregnancy T/SHBG ratio exhibits a potentially stronger correlation with fetal growth potential compared to SHBG alone. DHEAS and maternal age at delivery are strongly correlated in PCOS patients. Full article

Background/Objective: Infertility affects an estimated 40–50% of women with polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility, but only a small proportion of the patients require in vitro fertilization (IVF) therapy. Both PCOS and IVF are associated with an increased risk of obstetric complications. To compare preconception endocrine profiles and symptoms, as well as obstetric outcomes of PCOS patients who achieved successful pregnancies with and without IVF treatment. Methods: A single-center retrospective cohort study was conducted. Data spanning from 2012 to 2019 were compiled from patients with PCOS who visited the Gynecologic Endocrinology Unit and the Infertility Unit at the Department of Obstetrics and Gynecology, University of Debrecen. Patients diagnosed with PCOS who had had at least one successful delivery beyond the 23rd gestational week at the department were eligible for inclusion in the study. Results: Fifteen percent of the 206 pregnancies leading to successful deliveries of 232 newborns in our cohort conceived with IVF. A one year increase in the maternal age increased the odds of being in the IVF group by 22% (OR: 1.222, 95% confidence interval, CI: 1.11–1.35, p < 0.001). Baseline DHEAS and androstenedione levels were significantly lower in the IVF group as compared to the non-IVF group: 1 μmol/L increase in the DHEAS level decreased the odds of being in the IVF group by 18% (OR: 0.82, 95% CI: 0.66–1.01, p = 0.06), and 1 μg/L increase in the serum androstenedione concentration decreased the same odds by 42% (OR: 0.58, 95% CI: 0.33–1.02, p = 0.056). DHEAS levels <6.5 μmol/L had an OR 3.86 (95% CI 1.10–13.50, p = 0.04) and LH/FSH ratio <1.3 had an OR 3.58 (95% CI 1.18–10.81, p = 0.03) for being in the IVF group. The birth weight (3069 ± 683 g vs. 3362 ± 638 g, p = 0.02) and the gestational age (37.23 ± 2.55 vs. 38.54 ± 2.28 weeks, p = 0.004) were significantly lower in the IVF group, but in the singleton subgroups, no significant differences could be found. Birth weight percentiles showed no significant difference in either subgroup. In the IVF group, both preterm delivery (29% vs. 8.3%, OR 4.53, 95% CI 1.75–11.70, p = 0.002; singleton subgroup: 17.4% vs. 6.3%, OR 3.12, 95% CI 0.89–10.92, p = 0.07) and cesarean section (71% vs. 43.2%, OR 3.22, 95% CI 1.40–7.40, p = 0.006; singleton subgroup: 65.2% vs. 42.4%, OR 2.55, 95% CI 1.02–6.35, p = 0.04) were more frequent than in the non-IVF group. Gestational diabetes and preeclampsia were not significantly different in the IVF and non-IVF groups. Conclusions: In PCOS patients with successful pregnancies, those who conceive with IVF seem to be different in their baseline hormone levels and symptoms from the non-IVF group. Adverse obstetric outcomes are more common in the IVF group, and some of these differences persist when adjusting for singleton pregnancies and maternal age, too. Full article

The etiopathogenesis of preeclampsia, a leading hypertensive disorder of pregnancy, has been proposed to involve an abnormal circulating sex hormone profile and misexpression of placental estrogen and progesterone receptors (ER and PR, respectively). However, existing research is vastly confined to third trimester preeclamptic placentas. Consequently, the placental–uterine molecular crosstalk and the dynamic ER and PR expression pattern in the peri-conception period remain overlooked. Herein, our goal was to use the BPH/5 mouse to elucidate pre-pregnancy and early gestation Er and Pr dynamics in a preeclamptic-like uterus. BPH/5 females display low circulating estrogen concentration during proestrus, followed by early gestation hypoestrogenemia, hyperprogesteronemia, and a spontaneous preeclamptic-like phenotype. Preceding pregnancy, the gene encoding Er alpha (Erα, Esr1) is upregulated in the diestrual BPH/5 uterus. At the peak of decidualization, Esr1, Er beta (Erβ, Esr2), and Pr isoform B (Pr-B) were upregulated in the BPH/5 maternal–fetal interface. At the protein level, BPH/5 females display higher percentage of decidual cells with nuclear Erα expression, as well as Pr downregulation in the decidua, luminal and glandular epithelium. In conclusion, we provide evidence of disrupted sex hormone signaling in the peri-conception period of preeclamptic-like pregnancies, potentially shedding some light onto the intricate role of sex hormone signaling at unexplored timepoints of human preeclampsia. Full article

Background and Objectives: Graves’ disease (GD) and primary aldosteronism (PA) are two pathologies that can cause significant morbidity and mortality. GD is mediated by autoantibodies, and recent studies have shown autoantibody involvement in the pathophysiology behind both PA and pre-eclampsia. The coexistence of GD and PA, however, is reportedly rare. This report describes a unique case of Graves’ hyperthyroidism and concomitant PA in a patient with a history of pre-eclampsia with severe features. Case Presentation: The patient presented at 17 weeks pregnancy with mild hyperthyroidism, negative TSH receptor antibodies, and a low level of thyroid-stimulating immunoglobulins (TSI). Her TSH became detectable with normal thyroid hormone levels, and therefore, no anti-thyroid medication was administered. At 34 weeks she developed pre-eclampsia with severe features, and a healthy child was delivered; her TSH returned to normal. Seven months after delivery, she presented emergently with severe hyperthyroidism, hypertensive crisis, and a serum potassium of 2.5 mmol/L. Her hypertension was uncontrolled on multiple anti-hypertensives. Both TSI and TSH receptor antibodies were negative. The aldosterone(ng/dL)/renin(ng/mL/h ratio was (13/0.06) = 216.7, and abdominal CT imaging demonstrated normal adrenal glands; thus, a diagnosis of PA was made. Her blood pressure was subsequently controlled with only spironolactone at 50 mg 2xday. Methimazole was started but discontinued because of an allergic reaction. Consequently, a thyroidectomy was performed, and pathology revealed Graves’ disease. The patient remained well on levothyroxine at 125 mcg/day and spironolactone at 50 mg 2xday three months after the thyroidectomy. Conclusions: This patient manifested severe GD with antibodies undetectable by conventional TSI and TSH receptor assays and accelerated hypertension from PA simultaneously. These conditions were successfully treated separately by spironolactone and thyroidectomy. Autoimmune PA was considered likely given the clinical picture. The diagnosis of PA should be considered in hypertension with GD. Full article

Transforming growth factor beta (TGF-β), a multifunctional cytokine, is one of the most important inflammatory cytokines closely related to pregnancy. It plays significant roles in hormone secretion, placental development, and embryonic growth during pregnancy. TGF-β is implicated in embryo implantation and inhibits the invasion of extraepithelial trophoblast cells. It also moderates the mother-fetus interaction by adjusting the secretion pattern of immunomodulatory factors in the placenta, consequently influencing the mother’s immune cells. The TGF-β family regulates the development of the nervous, respiratory, and cardiovascular systems by regulating gene expression. Furthermore, TGF-β has been associated with various pregnancy complications. An increase in TGF-β levels can induce the occurrences of pre-eclampsia and gestational diabetes mellitus, while a decrease can lead to recurrent miscarriage due to the interference of the immune tolerance environment. This review focuses on the role of TGF-β in embryo implantation and development, providing new insights for the clinical prevention and treatment of pregnancy complications. Full article

(1) Background: The presence of adenomyosis among pregnant patients has been associated with a higher incidence of miscarriage and pregnancy complications. Although the role of adenomyosis in women undergoing in vitro fertilization (IVF) was investigated in several studies and demonstrated a potentially detrimental effect on live birth rates following IVF, most of them were small studies in which the adenomyosis diagnosis was not confirmed based on solid ultrasonographic criteria. (2) Methods: 3503 patients undergoing their first blastocyst frozen transfer through a hormonal replacement (HRT) FET cycle. Among them, 140 women had a confirmed diagnosis of adenomyosis based on the MUSA criteria. (3) Results: Adenomyosis patients were more likely to proceed with deferred FET compared with no-adenomyosis women (p = 0.002) and were significantly more likely to be treated with GnRH agonist pre-treatment (2 months) (p < 0.001). The presence of adenomyosis significantly decreased the clinical pregnancy rates (aOR 0.62, 95% CI: 0.39–0.98, p = 0.040) and live birth rates (aOR 0.46, 95% CI: 0.27–0.75, p = 0.003) and significantly increased the miscarriage rates (aOR 2.13, 95% CI: 0.98–4.37, p = 0.045). Multivariable logistic regression adjusting for age, autologous or donor oocytes, PGT-A, deferred FET, serum progesterone levels the day before FET, GnRH agonist pre-treatment, number of embryos transferred, and adenomyosis demonstrated that the use of the GnRH agonist protocol did not decrease or increase the miscarriage rate, clinical pregnancy rate, or live birth rate. (4) Conclusions: The presence of adenomyosis had a significant negative impact on the clinical outcomes of patients undergoing FET and was associated with higher miscarriage, lower clinical pregnancy, and live birth rates. GnRH agonist pre-treatment does not appear to improve clinical outcomes. Full article

Fetal programming provides explanatory mechanisms for the currently high prevalence of gestational obesity. The endocannabinoid system (ECS) participates in the regulation of energy balance, and with a high-fat diet (HFD), it is overactivated. The aim of this study was to determine the effects of a nutritional intervention during pregnancy and lactation on obese female progenitors, on metabolic alterations of the offspring and on the involvement of ECS. Female mice (C57/BL/6-F0), 45 days old, and their offspring (males) were separated according to type of diet before and during gestation and lactation: CON-F1: control diet; HFD-F1 group: HFD (fat: 60% Kcal); INT-F1 group: HFD until mating and control diet (fat: 10% Kcal) afterward. Glucose tolerance and insulin sensitivity (IS) were tested at 2 and 4 months. At 120 days, mice were sacrificed, plasma was extracted for the determination of hormones, and livers for gene expression and the protein level determination of ECS components. INT-F1 group presented a lower IS compared to CON-F1, and normal levels of adiponectin and corticosterone in relation to the HFD-F1 group. The intervention increased hepatic gene expression for fatty-acid amide hydrolase and monoacylglycerol lipase enzymes; however, these differences were not observed at the protein expression level. Our results suggest that this intervention model normalized some hormonal parameters and hepatic mRNA levels of ECS components that were altered in the offspring of progenitors with pre-pregnancy obesity. Full article

Pre-pregnancy weight gain induces dysregulation in the metabolic profile of the offspring, thereby serving as a key factor for cognitive decline and anxiety status in the offspring. However, early probiotic supplementation during the gestational period is linked with improved metabolic health. At the same time, a natural plant known as Elateriospermum tapos (E. tapos) is proven to improve cognition and modulate the stress hormone due to its high concentration of flavonoids. However, the effects of medicinal plant integrated probiotics in F1 generations warrants further investigation. Thus, this study aimed to study the effect of E. tapos yoghurt on the maternal obesity induced cognitive dysfunction and anxiety in female offspring. In this study, female Sprague Dawley rats were fed with normal chow (n = 8) or high fat diet (n = 40) across pre-pregnancy, gestation, and weaning. The treatment with different concentrations of E. tapos yoghurt (5, 50, and 500 mg/kg/day) were initiated in the obese dams upon post coitum day 0 up to postnatal day 21 (PND 21). Female offspring were weaned on PND 21 and body mass index, waist circumference, lee index, behavior, metabolic parameter, and antioxidant status were analyzed. The result shows that the female offspring of the 500 mg/kg E. tapos yoghurt supplemented group shows a decreased level of insulin, fasting blood glucose, cholesterol, triglycerides, LDL, low fat tissue mass with a high level of HDL, and an increased level of antioxidant status in the hypothalamus. The behavioral assessment proves that the female offspring of the 500 mg/kg E. tapos yoghurt supplemented group exhibits a high recognition index on novel object/place with low anxiety-like behavior in an open field test. In conclusion, our data signify the beneficial effect of early intervention in obese dams on the transgenerational impact on female offspring’s metabolic profile, cognitive performance, and anxiety-like behavior. Full article

Fetal adaptations to harmful intrauterine environments due to pregnancy disorders such as preeclampsia (PE) can negatively program the offspring’s metabolism, resulting in long-term metabolic changes. PE is characterized by increased circulating levels of sFLT1, placental dysfunction and fetal growth restriction (FGR). Here we examine the consequences of systemic human sFLT1 overexpression in transgenic PE/FGR mice on the offspring’s metabolic phenotype. Histological and molecular analyses of fetal and offspring livers as well as examinations of offspring serum hormones were performed. At 18.5 dpc, sFLT1 overexpression resulted in growth-restricted fetuses with a reduced liver weight, combined with reduced hepatic glycogen storage and histological signs of hemorrhages and hepatocyte apoptosis. This was further associated with altered gene expression of the molecules involved in fatty acid and glucose/glycogen metabolism. In most analyzed features males were more affected than females. The postnatal follow-up revealed an increased weight gain of male PE offspring, and increased serum levels of Insulin and Leptin. This was associated with changes in hepatic gene expression regulating fatty acid and glucose metabolism in male PE offspring. To conclude, our results indicate that sFLT1-related PE/FGR in mice leads to altered fetal liver development, which might result in an adverse metabolic pre-programming of the offspring, specifically targeting males. This could be linked to the known sex differences seen in PE pregnancies in human. Full article

One of the main causes of maternal and neonatal morbidity and mortality is pre-eclampsia. It is characterized by a high sFlt1/PlGF ratio, according to prior research. Pregestational diseases in mothers may increase the risk of developing pre-eclampsia. Only a few studies have looked at the connection between maternal comorbidities before conception and the sFlt1/PlGF ratio. The most recent information regarding the association between maternal pregestational diseases and the ratio of sFlt1/PlGF is described in this review. The paper also examines current research suggesting that changes in pregnancy hormones and metabolites are related to a high sFlt1/PlGF ratio. Certain maternal disorders have been found to dramatically raise sFlt-1 and sFlt1/PlGF levels, according to an analysis of the literature. There is still debate about the data on the association between the sFlt1/PlGF ratio and maternal disorders such as HIV, acute coronary syndromes, cardiovascular function in the mother between 19 and 23 weeks of pregnancy, thyroid hormones, diabetes, and cancer. Additional research is needed to confirm these findings. Full article

This study aimed to evaluate the effect of the ovarian status and steroid hormone concentration on the day of TAI on the reproductive performance of dairy cows subjected to estrus synchronization treatment and timed artificial insemination with sexed semen. Seventy-eight cyclic Holstein cows pre-treated with PGF2α-GnRH were divided in two groups—I (Preselect-OvSynch, n = 38) and II (OvSynch+PRID-7-day+eCG, n = 40)—and inseminated with sexed semen. The presence of preovulatory follicle (PF) with or without corpus luteum (CL), the PF diameter, the estradiol (E₂) and progesterone (P₄) concentrations on the day of TAI, the pregnancy rate (PR) and embryo loss were determined. On the day of TAI, 78.4% of all the pregnant cows presented a PF (mean size 1.80 ± 0.12 cm) without CL, low P₄ (0.59 ± 0.28 ng/mL) and high E₂ (12.35 ± 2.62 pg/mg) concentrations. The positive correlation between the size of the PF and the level of E₂ in the pregnant cows from group II was stronger than that of group I (R = 0.82 vs. R = 0.52, p < 0.05). The pregnancy rate on day 30 (57.5% vs. 36.8%) and day 60 (50% vs. 26.3%; p < 0.05) and the embryo losses (13% vs. 28.5%) showed better effects of treatment in group II. In conclusion, the ovarian status and the steroid hormone concentration on the day of TAI influence the pregnancy rates of dairy cows subjected to estrus synchronization and timed artificial insemination with sexed semen. Full article

Women affected by maternal pregestational diabetes mellitus (type 1 or type 2) or by polycystic ovary syndrome experience an increased risk of pregnancy complications, as well as suboptimal lactation outcomes. The hormone prolactin plays important roles in pregnancy and postpartum, both as a metabolic and lactogenic hormone. We aimed to explore, through a systematic review, the relationship between pregestational maternal metabolic conditions and prolactin levels in pregnancy and postpartum. MEDLINE via OVID, CINAHL Plus, and Embase were searched from inception to 9 May 2022. Eligible studies included women who were pregnant or up to 12 months postpartum and had a pre-existing diagnosis of type 1 or type 2 diabetes mellitus or polycystic ovary syndrome; with reporting of at least one endogenous maternal serum prolactin level during this time. Two independent reviewers extracted the data. Eleven studies met the eligibility criteria. The studies were too diverse and heterogeneous to enable meta-analysis. Overall, prolactin levels appeared to be lower in pregnancies affected by type 1 diabetes mellitus. There was little data in polycystic ovary syndrome or type 2 diabetes pregnancy, but prolactin increment across pregnancy in polycystic ovary syndrome emerged as an area for future study. During postpartum, lactation difficulties in women with metabolic disease present before pregnancy are well-described, but the relationship to prolactin remains unclear. Overall, preliminary evidence suggests that pre-existing maternal metabolic disease may alter prolactin dynamics in pregnancy and postpartum. Further well-designed studies in modern cohorts, with standardised collection and serial sampling across pregnancy and postpartum, are required to clarify these associations. Full article

The aims of this study were to characterize the exposure of pregnant women living in Portugal to 3-phenoxybenzoic acid (3-PBA) and to evaluate the association of this exposure with maternal outcomes and newborn anthropometric measures. We also aimed to compare exposure in summer with exposure in winter. Pregnant women attending ultrasound scans from April 2018 to April 2019 at a central hospital in Porto, Portugal, were invited to participate. Inclusion criteria were: gestational week between 10 and 13, confirmed fetal vitality, and a signature of informed consent. 3-PBA was measured in spot urine samples by gas chromatography with mass spectrometry (GC-MS). The median 3-PBA concentration was 0.263 (0.167; 0.458) µg/g creatinine (n = 145). 3-PBA excretion was negatively associated with maternal pre-pregnancy body mass index (BMI) (p = 0.049), and it was higher during the summer when compared to winter (p < 0.001). The frequency of fish or yogurt consumption was associated positively with 3-PBA excretion, particularly during the winter (p = 0.002 and p = 0.015, respectively), when environmental exposure is low. Moreover, 3-PBA was associated with levothyroxine use (p = 0.01), a proxy for hypothyroidism, which could be due to a putative 3-PBA—thyroid hormone antagonistic effect. 3-PBA levels were not associated with the anthropometric measures of the newborn. In conclusion, pregnant women living in Portugal are exposed to 3-PBA, particularly during summer, and this exposure may be associated with maternal clinical features. Full article